Favipiravir for Treatment of Outpatients With Asymptomatic or Uncomplicated Coronavirus Disease 2019: A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Trial.

BACKGROUND: Favipiravir, an oral, RNA-dependent RNA polymerase inhibitor, has in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite limited data, favipiravir is administered to patients with coronavirus disease 2019 (COVID-19) in several countries. METHODS: We conducted a phase 2, double-blind, randomized controlled outpatient trial of favipiravir in asymptomatic or mildly symptomatic adults with a positive SARS-CoV-2 reverse-transcription polymerase chain reaction assay (RT-PCR) within 72 hours of enrollment. Participants were randomized to receive placebo or favipiravir (1800 mg twice daily [BID] day 1, 800 mg BID days 2-10). The primary outcome was SARS-CoV-2 shedding cessation in a modified intention-to-treat (mITT) cohort of participants with positive enrollment RT-PCRs. Using SARS-CoV-2 amplicon-based sequencing, we assessed favipiravir's impact on mutagenesis. RESULTS: We randomized 149 participants with 116 included in the mITT cohort. The participants' mean age was 43 years (standard deviation, 12.5 years) and 57 (49%) were women. We found no difference in time to shedding cessation overall (hazard ratio [HR], 0.76 favoring placebo [95% confidence interval {CI}, .48-1.20]) or in subgroups (age, sex, high-risk comorbidities, seropositivity, or symptom duration at enrollment). We detected no difference in time to symptom resolution (initial: HR, 0.84 [95% CI, .54-1.29]; sustained: HR, 0.87 [95% CI, .52-1.45]) and no difference in transition mutation accumulation in the viral genome during treatment. CONCLUSIONS: Our data do not support favipiravir at commonly used doses in outpatients with uncomplicated COVID-19. Further research is needed to ascertain if higher favipiravir doses are effective and safe for patients with COVID-19. CLINICAL TRIALS REGISTRATION: NCT04346628.

Phantom urinary incontinence in children with bladder-bowel dysfunction.

OBJECTIVE: To report a previously undescribed condition in which children present with the sensation of wetness because of presumed urinary incontinence when they are actually completely dry. We have termed this entity "phantom" urinary incontinence (PUI). MATERIALS AND METHODS: Twenty children referred to our pediatric urology clinic were diagnosed with PUI between 2009 and 2013. Patient demographics, associated bladder and bowel symptoms, concomitant diagnoses, imaging, management, and treatment outcomes were evaluated. RESULTS: Twenty children (18 females and 2 males) were diagnosed with PUI over a 5-year interval. Mean age at diagnosis was 6.9 ± 2.5 years (range, 4-12 years). Nineteen patients (95%) had concomitant lower urinary tract symptoms, and all were also diagnosed with constipation. Urgency (75%) and frequency (50%) were the most common associated bladder symptoms. Of the 18 girls, 13 (72%) had associated vaginitis. Fourteen children (70%) carried a parent-reported diagnosis of obsessive-compulsive disorder or obsessive-compulsive disorder personality traits. Patients were managed with timed voiding, dietary modifications, and a bowel regimen. Ninety percent children experienced improvement of bladder-bowel dysfunction and resolution of PUI at a mean follow-up of 14.4 months. CONCLUSION: Children with PUI have a high incidence of obsessive-compulsive traits. Phantom incontinence as well as associated lower urinary tract symptoms resolve with adherence to a strict bladder-bowel regimen.

Effective endoscopic diagnosis and treatment of pediatric occult vesicoureteral reflux with intermediate to long-term follow-up.

PURPOSE: Recurrent febrile urinary tract infections (fUTIs) in children with non-diagnostic voiding cystourethrogram (VCUG) are challenging, as misdiagnosis can lead to renal damage and increased morbidity. We compared fUTI rates before and after endoscopic treatment of patients with suspected occult VUR. METHODS: Between January 2009 and December 2012, children with history of fUTI and non-diagnostic VCUG(s) underwent endoscopic ureteral hydrodistention (HD) and injection of dextranomer hyaluronic acid co-polymer (Dx/HA). fUTI rates before and after intervention were evaluated. Demographics, imaging and endoscopic findings were assessed. RESULTS: Thirty-four children (mean age 5.4±2.8 years) underwent bilateral Dx/HA injection for occult VUR. Average follow-up was 28.8 months. Seventeen children had renal scarring. Mean ureteral HD grade was 2.2/3. HD grade for ureters associated with renal scarring was significantly (p<0.05) higher (2.6/3) than those without scarring (2.0/3). Mean injected volume was 1.2 mL. Ureters associated with renal scarring (n=21) required significantly (p<0.05) higher volumes (1.4 mL) than those without scarring (n=47; 1.1 mL). Prior to intervention, the fUTI rate was 0.15/patient/month compared to just 0.02 after treatment (p<0.0001). CONCLUSIONS: Incidence of fUTIs significantly decreased following treatment, supporting the use of Dx/HA injection in carefully selected children when the suspicion for occult VUR is high.

Is endoscopic injection therapy a reasonable treatment option for low-grade vesicoureteral reflux in association with overactive bladder?

OBJECTIVE: To assess the clinical outcome of endoscopic injection in children with vesicoureteral reflux (VUR) and concomittant overactive bladder (OAB). METHODS: A total of 41 patients with VUR and OAB underwent endoscopic injection of dextranomer/hyaluronic acid. At surgery, 13 patients had been successfully treated for their OAB (urgency with or without wetting) with behavior modification with or without anticholinergic therapy, and 28 had persistent OAB despite treatment. Voiding cystourethrogram was obtained 6-12 weeks postoperatively, and patients were followed up clinically for 1-5 years. RESULTS: Negative voiding cystourethrogram findings after a single treatment were seen in 34 (82.9%) of 41 patients. The radiographic success rate in patients with well-controlled OAB was 76.9% (10 of 13) compared with 85.7% (24 of 28) of those with poorly controlled OAB. The overall clinical success rate, defined as no evidence of urinary tract infection in the setting of negative voiding cystourethrogram findings, reached 78.0% (32 of 41). After successful endoscopic treatment, an unanticipated return to normal voiding patterns without the need for postoperative anticholinergic therapy was seen in 4 of the children with well-controlled OAB (40.0%) and in 4 with poorly controlled OAB (16.7%). CONCLUSION: Our data suggest that endoscopic injection is a viable treatment option for VUR in those with OAB, with postoperative rates of resolution comparable to those found in patients without OAB. Furthermore, 40.0% of children with well-controlled OAB no longer required therapy for OAB after resolution of their VUR.